Presentation of my master thesis in Medical Physics at Heidelberg University.

1. Automatic analysis of angiogenic hotspots
in histological whole slide images
Master thesis in Medical Physics
by Jakob Nikolas Kather
supervised by: PD Dr. Frank Zöllner, Dr. Cleo-Aron Weis

2. Jakob Nikolas Kather I Slide 2 I 8/22/2015
• Pathophysiology: all solid
tumors need blood supply
• Example: Colorectal cancer
• More blood vessels correlate
to higher mortality
Tumor angiogenesis Introduction

3. Jakob Nikolas Kather I Slide 3 I 8/22/2015
Microscopy and blood vessel immunostaining Introduction

4. Jakob Nikolas Kather I Slide 4 I 8/22/2015
Colorectal cancer: whole slide imaging
2mm
Introduction

5. Jakob Nikolas Kather I Slide 5 I 8/22/2015
Aim of this study
Use image analysis to make this procedure
objective and reproducible
State of the art Introduction

6. Jakob Nikolas Kather I Slide 6 I 8/22/2015
Image segmentation Methods

7. Jakob Nikolas Kather I Slide 7 I 8/22/2015
Blood vessel map on whole slide image Methods

8. Jakob Nikolas Kather I Slide 8 I 8/22/2015
Comparison to random pattern Methods

9. Jakob Nikolas Kather I Slide 9 I 8/22/2015
Continuous density function Results

10. Jakob Nikolas Kather I Slide 10 I 8/22/2015
F(x,y)
x,y
ρ
μ
σ
obs
CSR
probability function
spatial dimensions
density function
global mean
global std. dev.
observed data
random data
Normalization / Noise removal Results

11. Jakob Nikolas Kather I Slide 11 I 8/22/2015
standard
deviations
Hotspot probability map Results

12. Jakob Nikolas Kather I Slide 12 I 8/22/2015
Black contours = hotspots selected by blinded observer (# primary hotspot)
Color bar refers to hotspot probability function overlay (* level of significance)
Comparison to human observer Results

13. Jakob Nikolas Kather I Slide 13 I 8/22/2015
Optimized workflow Conclusion

14. Jakob Nikolas Kather I Slide 14 I 8/22/2015
Multivariate maps Outlook

15. Jakob Nikolas Kather I Slide 15 I 8/22/2015
Thank you!
PD Dr. Frank Zöllner
Dr. Cleo-Aron Weis, MSc
Prof. Dr. Lothar Schad
Prof. Dr. Alexander Marx

16. Jakob Nikolas Kather I Slide 16 I 8/22/2015
Des Guetz G, Uzzan B, Nicolas P, Cucherat M, Morere JF, Benamouzig R, et al. Microvessel
density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of
the literature. Br J Cancer 2006;94(12):1823-32.
Baddeley, A., & Turner, R. (2005). Spatstat: an R package for analyzing spatial point
patterns. J Stat Softw, 12(6), 1–42.
Gelfand, A. E., Diggle, P., Guttorp, P., & Fuentes, M. (2010). Handbook of spatial statistics.
Boca Raton, FL, USA: CRC press.
Kather, J. N., Marx, A., Reyes-Aldasoro, C. C., Schad, L. R., Zöllner, F. G., & Weis, C.-A.
(2015). Continuous representation of tumor microvessel density and detection of
angiogenic hotspots in histological whole-slide images. Oncotarget. Epub ahead of print
2015 Jun 8.
References